Cellular Injury

Question 1

Cellular injury occurs when STRESS&raquo_space; Cell’s ability to adapt (Growth adaptations = hypertrophy, hyperplasia, atrophy, hypoplasia, metaplasia, dysplasia). However, it depends on the SEVERITY of the stress. For instance, decreased afferent blood flow to the kidney can result in a growth adaptation (lower stress severity) OR injury (higher stress severity). Provide both pathways.

Answer 1

1. LOW SEVERITY: ATHEROSCLEROSIS/FIBROMUSCULAR DYSPLASIA of renal artery -> Cut blood supply to the kidney SLOWLY/PROGRESSIVELY -> Decreased nutrients -> ATROPHY (growth adaptation)
2. HIGH SEVERITY: THROMBUS IN LEFT HEART -> Embolizes to renal artery -> ACUTE/RAPID kidney injury -> INJURY INFARCTION (death of kidney parenchyma)

Question 2

Injury is also dependent on TYPE OF CELL AFFECTED. What tissue is most susceptible to ischemic injury? Which is resistant?

Answer 2

NEURONS: Highly susceptible to ischemic injury (3-5min)

SKELETAL MUSCLE: Relatively more resistant

Question 3

What are 3 causes of HYPOXIA?

Answer 3

1. ISCHEMIA
2. HYPOXEMIA
3. DECREASED O2-CARRYING CAPACITY OF BLOOD

Question 4

Pt was exposed to smoke from fires, or exhaust from cars/gas heaters. What is the cause of hypoxia in this pt?

Answer 4

CO POISONING

Question 5

What is the classic finding of a CO POISONING pt?

Answer 5

CHERRY RED APPEARANCE OF SKIN

Reason: HGB so tightly bound by CO -> Reflects red light -> Deceptive bec pt looks RED BUT is actually hypoxic

Question 6

***What is the early sign of CO exposure? Later signs?

Answer 6

HEADACHE!

Later signs = COMA + DEATH (many pts use CO poisoning for suicide)

Question 7

What is the most commonly tested cause of METHEMOGLOBINEMIA? Which pt population is most susceptible?

Answer 7

1. DRUGS - SULFA, NITRATES

2. NEWBORNS - Lack oxidant-stress induced free radical REDUCING GLUTATHIONE system

Question 8

What is the classic presentation of METHEMOGLOBINEMIA?What is the pathology of METHEMOGLOBINEMIA? What is the treatment?

Answer 8

CYANOSIS + CHOCOLATE-COLORED BLOOD
Pathology: Normally, Fe2+ binds O2
Oxidant stress -> Oxidizes Fe2+ to Fe3+ -> Can no longer bind O2
Tx = IV METHYLENE BLUE - Reduces Fe3+ back to Fe2+

Question 9

CHERRY RED SKIN, HYPOXIC

CHOCOLATE COLORED BLOOD, HYPOXIC

Answer 9

CHERRY: CO POISONING HYPOXIA
CHOCOLATE: METHEMOGLOBINEMIA

Question 10

What is the hallmark of the INITIAL PHASE of cellular injury (REVERSIBLE)?

Answer 10

CELLULAR SWELLING

Hypoxia -> Impaired oxidative phosphorylation -> Decreased ATP -> Na+/K+ ATP-ase impaired -> INCREASED Intracellular Na+ -> Water follows inside cell = SWELLING

Question 11

What are 3 histologic features of CELLULAR SWELLING as a hallmark of REVERSIBLE CELLULAR INJURY?

Answer 11

1. LOSS OF MICROVILLI in renal PCT, small bowel (Think of blowing air into surgical glove -> Fingers [villi] start to disappear)
2. MEMBRANE BLEBBING: Cellular swelling -> Loss of cytoskeletal integrity to the membrane -> Membrane starts blebbing
3. DISSOCIATION OF RIBOSOMES: Rough ER swelling -> Dissociation of loosely associated ribosomes -> Decreased protein synthesis

Question 12

What is the hallmark of IRREVERSIBLE CELLULAR INJURY? What are the 3 most common affected areas?

Answer 12

MEMBRANE DAMAGE **

1. PLASMA MEMBRANE
2. MITOCHONDRIAL MEMBRANE
3. LYSOSOMAL MEMBRANE

Question 13

What are the results of the 3 membrane damages in IRREVERSIBLE CELLULAR INJURY?

Answer 13

1. PLASMA MEMBRANE DAMAGE: Leakage of cytosolic enzymes (e.g. troponins, ALT/AST, pancreatic enzymes) + Ca2+ influx (normally cytosolic Ca2+ kept low to prevent activation of enzymes by Ca2+ ATP-ase)
2. MITOCHONDRIAL MEMBRANE DAMAGE: Loss of ETC (inner mitochondrial membrane) resulting in decreased ATP (Ox/Phos) + Cytochrome C leakage activating caspases and APOPTOSIS
3. LYSOSOMAL MEMBRANE DAMAGE: Leakage of hydrolytic enzymes into cytosol/ Intracellular Ca2+ activating these enzymes -> AUTODIGESTION of cell itself

Question 14

What is the end result of IRREVERSIBLE CELL DAMAGE?

Answer 14

CELL DEATH